The main theme of the proposed research will remain the regulation of metabolic processes, with special reference to pathological situations such as diabetes, metabolic acidosis, effects of ethanol, hypoxia associated chronic respiratory disease and heart failure. In the centre of interest are gluconeogenesis, ketogenesis, caloric homeostasis, maintenance and de novo synthesis of adenine nucleotides and the regulation of the redox state of the pyridine nucleotides. A major part of the research will be directed to the interactions of amino acid and carbohydrate metabolism with special emphasis on amino acids as regulators of gluconeogenesis from non-nitrogenous precursors. The main techniques to be used will involve isolated liver perfusion, preparations of isolated liver cells and of isolated kidney tubules, in combination with the determination of metabolites in the intracellular and extracellular compartments. The technique of freeze-clamping will be used in in vivo experiments. The chief experimental animal will be the rat. Experience gained in the maintenance of functional integrity of the isolated perfused organ and in isolated cells will be used in studies of problems connected with organ transplantation.